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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metformin's hypolipidemic effects (2.55 g/day for 3 months) have been studied in 19 subjects with Fredrickson's Type IV hyperprebetalipoproteinemia. The majority of patients were above ideal body weight (relative body weight = 118 +/- 2.7 %). Eleven of the subjects presented chemical diabetes, 5 fasting hyperglycemia, and 3 normal glucose tolerance. After treatment with metformin, body weight showed a slight, but significant reduction (--2.4 +/- 0.3 kg). Glucose tolerence was not substantially altered while basal glucose was significantly reduced in the 5 subjects with fasting hyperglycemia. Basal plasma insulin was significantly reduced in all the patients following metformin treatment. Insulin response to OGTT was slightly reduced in the subjects with fasting hyperglycemia. Independent of the patients' glucose tolerance, metformin treatment induced a marked decrease in plasma triglycerides (-- 40 %) and a reduction in plasma cholesterol (-- 12 %). No correlation was found between triglyceride and cholesterol reduction and body weight, glucose, and plasma insulin variations. Like phenformin, metformin acts not only on glucose metabolism and insulin secretion but on lipid metabolism as well.
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PMID:Hypolipidemic effects of metformin in hyperprebetalipoproteinemia. 18 98

In a survey, the pharmacological and clinical documentation of metformin is presented and discussed, and the present state of knowledge relating to metformin-associated lactic acidosis is reviewed. The use of metformin in the treatment of diabetes is based on clinical experience over twenty years. It has been well documented that metformin is effective in maturity-onset diabetes both as monotherapy and in combination with a sulphonylurea. An advantage of metformin treatment is the tendency to weight reduction and the absence of significant hypoglycaemia; blood glucose levels are reduced only to normal. The disadvantages are the gastro-intestinal side effects and the potential risk of vitamin B 12 and folic acid deficiency during long-term use. Metformin-associated lactic acidosis is a very rare complication, which has mainly occured in patients with serious renal insufficiency or other contra-indications to the use of metformin. The association between phenformin and lactic acidosis has led to withdrawal of this biguanide in several countries. Metformin differs from phenformin in certain important respects, and the normal use of metformin does not involve the risk of side effects disproportionate to the intended effect. Further experimental studies are required to substantiate pharmacokinetics and metabolic effects of metformin in man.
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PMID:Metformin: a review of its pharmacological properties and therapeutic use. 38 88

Hyperglycemic obese and hyperinsulinemic mice of DBM strain develop a diabetic syndrome which can be compared to human maturity onset diabetes. In this study 6 to 49 weeks old female mice were used. Hyperglycemia and concomitant obesity were observed at 9 weeks. Plasma immunoreactive insulin (IRI) was maximum at 15--20 weeks, then decreased progressively with broad individual variations. Metformin, administered at 200 mg/kg per os, ineffective dosage in normal mice, showed a strong hypoglycemic effect in younger mice (11--18 weeks) with a plasma IRI decrease and no blood lactate and liver glycogen alteration. Plasma metformin concentration curve showed an exponential elimination fitted to a one compartment model with a plasma half-life of 2.7 hours. Metformin-induced hypoglycemia was lower in older mice (23--29 weeks) and corroborated their lower initial plasma IRI. All these results are in accordance with those reported in man and show that DBM mice provide a suitable model for a better understanding of antidiabetic drugs effects.
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PMID:DBM mice as a pharmacological model of maturity onset diabetes. Studies with metformin. 52 68

Platelet clumping was examined in untreated insulin-dependent and insulin-independent diabetics, with and without retinopathy. Hyperaggregation was noted, particularly in subjects with retinopathy and longstanding diabetes. Metformin normalised clumping in the course of mild diabetes.
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PMID:[Preliminary findings on 2 groups of diabetics with regard to platelet aggregation in relation to retinopathy and ultimate relation to antidiabetic therapy]. 66 85

The insulin and glucagon responses to arginine infusion were investigated in patients with maturity-onset diabetes under control conditions and during metformin therapy. Metformin did not significantly affect the insulin nor the glucagon response to arginine. These data support the concept that biguanide do not act directly on the islets of Langerhans.
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PMID:Influence of metformin on arginine-induced glucagon secretion in human diabetes. 123 63

Hyperglycaemia in patients with non-insulin-dependent diabetes mellitus (NIDDM) results from impaired insulin action and/or deficient insulin secretion. These abnormalities lead to increased hepatic glucose production, the primary cause of fasting hyperglycaemia, and decreased peripheral glucose uptake, the major mechanism responsible for postprandial hyperglycaemia. Hyperglycaemia in patients with NIDDM can be decreased by several different mechanisms: (1) a decrease in nutrient ingestion; (2) an increase in insulin secretion; (3) a decrease in hepatic glucose production; (4) an increase in peripheral glucose uptake. Oral agents used to treat NIDDM operate through 1 or more of the above mechanisms. alpha-Glucosidase inhibitors, a new class of drugs that delay carbohydrate digestion and absorption, reduce postprandial glycaemic rises by about 3 mmol/L. Metformin decreases fasting and postprandial hyperglycaemia through increasing glucose uptake and perhaps decreasing appetite. Sulphonylureas lower hyperglycaemia by increasing insulin secretion and to a lesser degree potentiating insulin action on the liver and peripheral tissues. alpha-Glucosidase inhibitors are particularly useful as primary therapy for patients with mild to moderate hyperglycaemia and in those patients who may be at risk for hypoglycaemia or lactic acidosis. Sulphonylureas are indicated for the more severely hyperglycaemic NIDDM patients who are not yet candidates for insulin therapy. Metformin is useful in obese moderately hyperglycaemic NIDDM patients. These oral agents can be used in combination to give better glycaemic control than is possible with each alone.
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PMID:Oral antidiabetic agents. The emergence of alpha-glucosidase inhibitors. 128 May 74

The main biguanides, metformin and phenformin, were introduced in 1957 as oral glucose-lowering agents to treat non-insulin-dependent diabetes mellitus (NIDDM). Phenformin was withdrawn in many countries because of an association with lactic acidosis, but metformin does not have the same risk if appropriately prescribed. Metformin is now widely used as a monotherapy and in combination with a sulfonylurea. Unlike sulfonylureas, metformin is not bound to plasma proteins, is not metabolized, and is eliminated rapidly by the kidney. The glucose-lowering effect occurs without stimulation of insulin secretion and results mainly from increased glucose utilization. The presence of insulin is required, and enhancement of insulin action at the postreceptor level occurs in peripheral tissues such as muscle. In peripheral tissues metformin increases insulin-mediated glucose uptake and oxidative metabolism. Metformin also increases glucose utilization by the intestine, primarily via nonoxidative metabolism. The extra lactate produced is largely extracted by the liver and serves as a substrate to sustain gluconeogenesis. This limits the extent to which metformin reduces hepatic glucose production but provides a safeguard against excessive glucose lowering. Because metformin does not cause clinical hypoglycemia, it is actually an antihyperglycemic drug. It does not cause weight gain, it helps combat hypertriglyceridemia, and it has been ascribed some vasoprotective properties. Metformin offers a useful treatment for insulin-resistant overweight NIDDM patients.
Diabetes Care 1992 Jun
PMID:Biguanides and NIDDM. 160 Aug 35

To examine the cellular mechanism of the antihyperglycemic action of metformin, we studied its effect on various functional and molecular parameters involved in the pathogenesis of insulin resistance. Isolated rat adipocytes were incubated with or without metformin (1-100 micrograms/ml) for 2 h at 37 degrees C followed by an incubation with or without insulin (1.72 nM). Metformin treatment had no significant effect on basal 3-O-methylglucose uptake. In contrast, metformin increased insulin-stimulated glucose transport in a dose-dependent manner up to 43 +/- 7%. This effect was neither associated with a significant effect of metformin on trace insulin binding (1.74 +/- 0.20% without metformin vs. 1.89 +/- 0.30% with metformin; P greater than 0.05) nor with an effect of metformin on insulin-receptor kinase activity as measured by 32P incorporation into the 95,000-Mr beta-subunit of the insulin receptor and an exogenous substrate, histone 2B.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Jul
PMID:Association of Metformin's effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes. 164 95

Two main classes of oral hypoglycaemic drugs, the sulphonylureas and the biguanides, are currently used in the therapy of type II, non-insulin-dependent diabetes mellitus (NIDDM). The basic pharmacokinetic properties of these agents are discussed with a view to efficient and safe treatment. Both first- and second-generation sulphonylureas are rapidly absorbed from the gastrointestinal tract. In the plasma compartment, these drugs are strongly bound to serum proteins. All sulphonylureas are metabolised in the liver, and the metabolites and the parent drugs are eliminated mainly in the urine, but also (second-generation derivatives) in the faces. Rapid- and short-acting sulphonylureas may improve early insulin release and promote better postprandial glucose control. Long-acting derivatives may ensure better control of overnight glycaemia. The elderly are at risk of developing severe sulphonylurea-induced hypoglycaemia, and in this population the agent chosen should have a short or intermediate duration of action and no active metabolites. Caution is needed when prescribing any sulphonylurea in patients receiving drugs known to affect sulphonylurea action, and in those with impaired liver and/or kidney function. The bioavailability of the biguanides ranges from 40 to 60%. Binding to plasma proteins is absent or very low. Metformin and buformin are not metabolised and are excreted in the urine; phenformin undergoes hepatic hydroxylation and is excreted in both urine and faeces. Metformin is the only agent of this class currently recommended for clinical use. The main indications of metformin treatment are NIDDM associated with obesity and/or hyperlipidaemia, and in combination with sulphonylurea both as primary treatment and when secondary failure occurs with sulphonylurea alone. Lactic acidosis may develop in patients receiving therapy with biguanides, especially in the presence of a preexisting contraindication to their use.
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PMID:Pharmacokinetic optimisation of oral hypoglycaemic therapy. 176 Sep 2

Using measurements of fibrin fibre thickness (microT) derived from turbidity and permeability (tau) of clotted plasma, it has been found that glucose in vitro added to plasma decreases permeability of the network despite unaltered fibrinogen conversion. Fibrin fibre thickness (microT) in uncontrolled diabetes is found significantly reduced. In diabetic plasma the degree of conversion to fibrin is similar to that in age and sex matched plasma from non-diabetics: the effect on fibrin network and fibre thickness probably arises from glycosylation of fibrinogen. Studies with Gliclazide, Metformin, Glibenclamide and insulin have shown that while all other drugs tested have no effect, Gliclazide increases fibrin fibre thickness (microT) significantly, diminishes tensile strength and reduces permeability. In separate experiments lysability of 125I-labelled fibrin networks developed in the presence of all four hypoglycaemic agents by tissue activator was tested. Networks developed in the presence of Metformin were found to lyse more quickly, followed by insulin and Gliclazide. Alterations induced in fibrin networks in diabetes may be nullified by some oral hypoglycaemic agents such as Gliclazide and not by others. Whether nullification of such changes has long-term effects in reducing the incidence of vascular disease in diabetics remains to be established.
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PMID:Studies on fibrin network structure in human plasma. Part II--Clinical application: diabetes and antidiabetic drugs. 178 32


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